The Longer Read: Acadia Postpones UK Plan for Daybue: What It Means — and What It Doesn’t
We recently learned that Acadia Pharmaceuticals has decided to postpone indefinitely its plans to seek UK regulatory or reimbursement approval for Daybue (Trofinetide).
In an interview, their CEO pointed to “high taxes and reimbursement challenges” as central obstacles. While those are real and significant, they are not the whole story—and they do not reflect the difficulties or promise facing all other potential Rett therapies.
We know this won’t be very reassuring for families who are keen for any treatment for their loved one with Rett syndrome. We want to explain what may lie behind this decision, put it in context with other drug approval stories, and reassure you that this is not a sign that the pipeline is dead.
What Acadia Claims — and What Lies Beneath
In reports, Acadia cited two headline barriers:
- High payback tax / rebate burden: The UK’s Voluntary Scheme for Branded Medicines Pricing, Access and Growth (VPAG) demands that branded drug manufacturers pay back a significant percentage of sales to the NHS. In the interview, Acadia claims rates near 23 % (far higher than in many European peers) make UK commercial launches economically untenable for smaller companies.
- Reimbursement / access uncertainty: Acadia’s CEO said that without reliable reimbursement pathways (i.e. confidence that the NHS will pay for the drug), they cannot commit to UK market entry.
In short, the cost structure and regulatory/market dynamics make UK unattractive for their projections.
But beyond those official statements, we see several additional risks and structural factors that may have influenced the decision. Some of them are particularly relevant to how rare disease drugs, especially those for Rett syndrome, are judged in the UK.
Hidden Risks & Structural Barriers
A) Modest efficacy / uncertain clinical benefit in many patients
From RSRT’s “Daybue: Key Facts for Parents” summary, we know that in the LAVENDER™ trial a majority of patients (≈61 %) were rated as showing “no change” on the primary clinical global impression measure; only ~13 % were “much improved” and no symptom-level breakdown was fully published.
In long-term or extension data, a significant fraction of patients discontinued.
These signals suggest that while there is benefit for some, the effect size is modest in many, making it harder to justify extremely high cost to payers.
Further, in published academic reviews, Trofinetide has shown statistically significant improvement in metrics like CGI-I and RSBQ in pediatric and adult Rett patients, but the magnitude of change is not always dramatic, and side-effects (especially GI issues) remain non-trivial. (PMC)
That means UK regulators and NICE will scrutinise benefit vs risk carefully, not just accept FDA decisions.
B) High cost relative to benefit & cost-effectiveness constraints
At approximately $500,000+ per year (or more) in the United States, Daybue’s proposed price is extremely high. Even putting aside the 23 % rebate/return burden in the UK, negotiating a price point that would satisfy NICE’s cost-effectiveness thresholds is extremely challenging. In the UK system, if a drug cannot demonstrate sufficient benefit (incremental survival, quality-of-life gains, disability reduction) relative to its cost, NICE simply may not recommend it — or require a heavily discounted/managed access scheme.
NICE already supports patient access schemes (PAS) — confidential discounts or usage-based pricing arrangements — precisely to allow high-cost drugs to become acceptable to the NHS when nominal list price would otherwise fail cost-effectiveness thresholds. (NICE)
But to win those, a company must accept tight constraints, possibly limited uptake, rigorous data demands, and ongoing risk.
C) Regulatory, logistical, and scalability burden
Launching in the UK is not just about having a licence; it demands infrastructure: post-marketing studies, pharmacovigilance, distribution, patient monitoring, and data generation. For smaller companies, that burden is non-trivial. If Acadia judges that the UK is a small or risky revenue market relative to the operational overhead, they may delay or opt out.
Also, delays or duplication in regulatory reviews, complexities in the UK’s NHS system, and the sheer fragmentation of commissioning (across regions, NICE, national specialised commissioning budgets) may add cost and friction.
D) Precedent of terminated NICE appraisals & withdrawal decisions
Over the past decade, industry has seen increasing numbers of terminated NICE appraisals — cases where a company obtains regulatory approval (e.g. via MHRA) but then chooses not to submit for NICE review, effectively halting access into the NHS. Analysts see this as a signal that many view UK reimbursement as too risky or unattractive.
Therefore, Acadia may have anticipated a high risk of rejection or withdrawal even before submitting.
Additionally, the UK’s constrained healthcare budget means payers must be selective. Even among “innovative” therapies, only those with strong data, compelling health economic models, and strategic partnerships tend to clear the hurdles.
But This Is Not a Signal of Doom for the Rett Pipeline
We want to be clear: this setback with Daybue’s UK plans does not doom all Rett therapies, nor does it mean future candidates will fail. Several reasons support optimism:
- Other therapies may have stronger efficacy signals, better safety profiles, or more leverage in negotiating pricing or managed access strategies.
- The UK has a separate Highly Specialised Technologies (HST) pathway (for ultra-rare, severe conditions with very high cost thresholds) that can employ more flexible cost-effectiveness thresholds. (GOV.UK)
- Some high-cost innovative treatments have succeeded in UK/NICE, even with massive price tags, when the evidence base and negotiation strategy were compelling.
Examples of high-cost drugs that cleared UK / NICE hurdles:
- Some cancer therapies with high list prices have been approved by NICE (often via patient access schemes and outcome-based deals) because their benefits justified the cost under negotiated terms.
- In certain rare disease areas, ultra-specialised therapies have gained approval where compelling efficacy, unmet need, and real-world evidence supported the case (though each example is unique in context).
- As the landscape evolves, NICE has shown in recent years some willingness to accept higher incremental cost-effectiveness ratios, especially for transformative therapies in high unmet need settings. (The Lancet)
We’ll continue to monitor examples and precedents to advocate for the strongest possible negotiating position for Rett therapies.
What This Means for Families & What We Are Doing
To families who feel discouraged, we empathise deeply. But here’s how we at Reverse Rett are responding and what we believe you can hold on to:
- We will continue engaging with UK regulators, policymakers, patient organisations, and payers to reduce structural barriers to future therapy launches.
- We will advocate strongly for transparent pricing models, patient access schemes, and regulatory pathways that recognise the severe unmet need in Rett.
- We will focus our efforts and spotlight on newer therapies that may have stronger data or more favorable economics.
- We will keep you informed, involved, and prepared: when a future therapy is ready, the UK Rett community will be more resilient, organised, and compelling in its case.
Final Thoughts
The news that Acadia is postponing UK plans for Daybue is disappointing but not unexpected in a challenging global environment. The decision is driven by a mix of high cost, modest efficacy, structural tax/rebate burdens, and reimbursement risk—not simply by one factor alone.
Let this be a sober reminder of how tough the UK system can be, but not a reason to lose hope. The Rett therapeutic pipeline remains alive. More advanced gene therapies, alternative small molecules, or combination approaches may bring better efficacy signals or more robust economic models. The path will be hard, but it’s far from closed.
We stand committed to pushing through the barriers, advocating tirelessly, and working toward a future where UK patients do not lose out because of systems that fail to recognise the urgency and potential of Rett treatments.